|Publication number||US6753017 B2|
|Application number||US 09/986,116|
|Publication date||Jun 22, 2004|
|Filing date||Nov 7, 2001|
|Priority date||Nov 7, 2001|
|Also published as||CN1326517C, CN1582144A, EP1443909A1, US20030086982, US20030104076, WO2003039515A1|
|Publication number||09986116, 986116, US 6753017 B2, US 6753017B2, US-B2-6753017, US6753017 B2, US6753017B2|
|Inventors||Wilhelm Berkulin, Karl-Hans Theissing|
|Original Assignee||Jrs Pharma Lp|
|Export Citation||BiBTeX, EndNote, RefMan|
|Patent Citations (33), Non-Patent Citations (3), Referenced by (13), Classifications (22), Legal Events (8)|
|External Links: USPTO, USPTO Assignment, Espacenet|
The present invention relates to a process for preparing dry extracts.
Extracts from plants or plant parts are widely employed in the food and drug fields. In many cases, it is appropriate to dry the thus obtained extracts in order the volume of the extracts. As far as other auxiliary agents are needed for the further processing of the dry extract, these are usually admixed with the liquid extract, followed by commonly drying them. Depending on what use is intended for the thus obtained dry products, further processing steps, such as wet granulation, fluidized-bed drying, compaction etc., can follow.
It has been the object of the present invention to provide a particularly simple process for adding further substances to an extract to be dried.
According to the invention, this object is achieved by a process for preparing dry extracts from a liquid extract and at least one additional substance by a spray-drying process, wherein said at least one additional substance is added to the spray-drying process in a dry form during the spray-drying process.
The wet extract droplets formed by the spraying will mix with said at least one additional substance and are dried on their common way through the spray-dryer, The residual moisture is generally below 5%.
Surprisingly, in this way, a homogeneous free-flowing powder can be obtained, which can be used, for example, directly for tabletting. Such a product is superior to both one obtained by commonly drying a solution of the extract and auxiliary agent, and one obtained by adding the auxiliary agent to the dried extract, with respect to galenic properties, especially tabletting property. Thus, the proportion of auxiliary agent can be significantly reduced as compared to conventional processes, so that smaller tablets can be produced with the same load of active substance, or more active substance can be introduced in predetermined tablet sizes.
The process is particularly useful if the liquid extract is the extract of a medicinal plant whose extract is to be administered in the form of tablets.
Said at least one additional substance will then be a galenic auxiliary agent. Galenic auxiliary agents are known to the skilled person. There may be mentioned, for example, lactose, maltodextrin, dextrin, dry glucose, starch, microcrystalline cellulose, silicated microcrystalline cellulose, Povidone®, polyethylene glycol, calcium phosphate, magnesium stearate, precipitated silicic acid, precipitated silica, highly dispersed silica, sorbitol, mannitol, or mixtures thereof.
The particle size of the additional substance employed is of less importance. Suitable particle sizes are within a range of from 1 to 500 μm.
The process according to the invention results in adhesion of the auxiliary agents to the extracts. Therefore, the invention also relates to the dry extract thus obtained, and to a medicament containing the dry extract according to the invention.
Preferably, the medicament according to the invention is a medicament in a tablet form.
For performing the process, a usual spray-drying plant can be used in which the liquid extract is introduced into a spray tower and drying air is simultaneously fed. By spraying into a hot-air current, the liquid products are quickly and mildly dried within seconds or fractions of seconds. The liquid extract to be dried typically contains from 5 to 70% of dry substance and is introduced into the spray tower at a pressure within a range of from 10 to 150 bar through one or more high-pressure nozzles. Usually, the temperature of the fed-in drying air is between 120 and 350° C., In the process according to the invention, the dry additional substance or a mixture of such substances is also introduced into the spray tower using blow conveyance, preferably in the vicinity of the spraying nozzles for the liquid extract.
For example, the design could be as follows:
A liquid extract is provided in a storage vessel. On a second position, there are dosing scales with the additional substance employed according to the invention in a dry form. The liquid extract is sprayed in together with the finely powdered additional substance at the top of the spray tower through high-pressure nozzles using a pump. Hot air is introduced into the spray tower from below. The exhaust air leaves at the top end of the spray tower and is optionally conducted to a heat exchanger. The dried product is conducted onto a vibrating bed at the lower end of the spray tower and introduced into the further production process. Alternatively, the product may be fed into a cyclone.
146.5 kg of St. John's wort extract having a dry content of 47.8% was spray-dried together with 30.00 kg of silicated microcrystalline cellulose at an air entry temperature of 210° C. and under a nozzle pressure of 40 bar to obtain 93.6 kg of dry product.
5236.8 kg of St. John's wort extract having a dry content of 38% was spray-dried together with 104.6 kg of highly dispersed silica at an air entry temperature of 200° C. and under a nozzle pressure of 90 bar to obtain 2065.8 kg of dry product.
1819.9 kg of Giant or Late Goldenrod extract having a dry content of 30% was spray-dried together with 221.7 kg of maltodextrin and 23.4 kg of highly dispersed silica at an air entry temperature of 215° C. and under a nozzle pressure of 45 bar to obtain 733.6 kg of dry product.
1640.00 kg of valerian root extract having a dry content of 51.8% was spray-dried together with 332.00 kg of dry glucose and 48.6 kg of highly dispersed silica at an air entry temperature of 230° C. and under a nozzle pressure of 80 bar to obtain 1142.8 kg of dry product.
658.5 kg of nettle root extract having a dry content of 32% was spray-dried together with 52.7 kg of lactose at an air entry temperature of 220° C. and under a nozzle pressure of 50 bar to obtain 262.4 kg of dry product.
|Cited Patent||Filing date||Publication date||Applicant||Title|
|US2756177||Mar 9, 1953||Jul 24, 1956||Hoffmann La Roche||Process for making fat-soluble vitamin active powder|
|US4395491 *||Feb 13, 1981||Jul 26, 1983||Hoechst Aktiengesellschaft||Method for isolating solid matter from a salinomycin culture broth|
|US4519961 *||Aug 30, 1982||May 28, 1985||Basf Aktiengesellschaft||Production of dry powders of substances which are sensitive to oxidation|
|US4533674||Oct 24, 1983||Aug 6, 1985||Basf Wyandotte Corporation||Process for preparing a sugar and starch free spray-dried vitamin C powder containing 90 percent ascorbic acid|
|US5466452||Feb 28, 1992||Nov 14, 1995||Phytopharm Ltd.||Pharmaceutical compositions for the treatment of skin disorders|
|US5585115||Jan 9, 1995||Dec 17, 1996||Edward H. Mendell Co., Inc.||Pharmaceutical excipient having improved compressability|
|US5709880||Jul 10, 1995||Jan 20, 1998||Buckman Laboratories International, Inc.||Method of making tabletized ionene polymers|
|US5725883||Jun 7, 1995||Mar 10, 1998||Edward Mendell Co., Inc.||Pharmaceutical excipient having improved compressibility|
|US5725884||Sep 30, 1996||Mar 10, 1998||Edward Mendell Co., Inc.||Pharmaceutical excipient having improved compressibility|
|US5733578||Nov 15, 1995||Mar 31, 1998||Edward Mendell Co., Inc.||Directly compressible high load acetaminophen formulations|
|US5741524||Jul 8, 1996||Apr 21, 1998||Edward Mendell Co., Inc.||Sustained-release formulations utilizing pharmaceutical excipient having improved compressibility|
|US5798101||May 1, 1997||Aug 25, 1998||Hpf, L.L.C.||Herbal appetite suppressant and weight loss composition|
|US5858412||Dec 17, 1997||Jan 12, 1999||Edward Mendell Co., Inc.||Sustained release formulations utilizing pharmaceutical excipient having improved compressibility with modified microcrystalline|
|US5866166||Jun 10, 1996||Feb 2, 1999||Edward Mendell Co., Inc.||Pharmaceutical excipient having improved compressibility|
|US5965166||Nov 5, 1997||Oct 12, 1999||Edward Mendell Co., Inc.||Directly compressible high load acetaminophen formulations|
|US6030645||Feb 20, 1998||Feb 29, 2000||Roche Vitamins Inc.||Free-flowing dry particles|
|US6103219||Dec 17, 1997||Aug 15, 2000||Edward Mendell Co., Inc.||Pharmaceutical excipient having improved compressibility|
|US6106865||Mar 10, 1998||Aug 22, 2000||Edward Mendell Co., Inc.||Pharmaceutical excipient having improved compressibility|
|US6153220||Sep 30, 1998||Nov 28, 2000||Elan Corporation, Plc||Taste-masked formulations|
|US6190696||Jun 7, 1999||Feb 20, 2001||Pieter J. Groenewoud||Stabilized thyroxine medications|
|US6217907||May 13, 1999||Apr 17, 2001||Edward Mendell Co., Inc.||Directly compressible high load acetaminophen formulations|
|US6217909||Nov 12, 1999||Apr 17, 2001||Edward Mendell Co., Inc.||Pharmaceutical excipient having improved compressibility|
|US6358533||Jan 4, 2001||Mar 19, 2002||Edward Mendell, Co., Inc.||Pharmaceutical excipient having improved compressibility|
|US6383526||Jul 21, 2000||May 7, 2002||Ancile Pharmaceuticals, Inc.||Process for the extraction of valerian root|
|US6391337||Mar 2, 2001||May 21, 2002||Edward Mendell Co., Inc.||Directly compressible high load acetaminophen formulations|
|US6395303||Jun 4, 1997||May 28, 2002||Edward Mendell Co., Inc.||Process for preparing a directly compressible solid dosage form containing microcrystalline cellulose|
|US6447815 *||Dec 19, 2000||Sep 10, 2002||Access Business Group International Llc||Heated alcohol extraction of herbs|
|US6521261||Oct 16, 2001||Feb 18, 2003||Edward Mendell Co., Inc.||Pharmaceutical excipient having improved compressibility|
|CN1311016A||Jan 21, 2001||Sep 5, 2001||程志清||Traditional Chinese medicine for curing viral myocarditis and its preparing process|
|EP0419308A2 *||Aug 29, 1990||Mar 27, 1991||Léon Georges Chevance||Use of glutamic acid or gum arabic as anti-complement agent|
|GB417552A||Title not available|
|GB1098065A||Title not available|
|WO1999015155A1||Sep 18, 1998||Apr 1, 1999||Leiras Oy||Pharmaceutical preparation comprising clodronate as active ingredient and silicified microcrystalline cellulose as excipient|
|1||Database WPI Section Ch, Week 200205, Class B04, AN 2002-034992 ZP002228002 Derwent Publications Lt., London, GB.|
|2||Editor: Budavari S.: "The Merck Index, 12<th >Edition", 1996, XP002227695, p. 1712, paragraph 10159 Merck and Co., Whitehouse Station, NJ., USA.|
|3||Editor: Budavari S.: "The Merck Index, 12th Edition", 1996, XP002227695, p. 1712, paragraph 10159 Merck and Co., Whitehouse Station, NJ., USA.|
|Citing Patent||Filing date||Publication date||Applicant||Title|
|US7879382||Sep 28, 2006||Feb 1, 2011||Fmc Corporation||Stabilizers and compositions and products comprising same|
|US7998505||Aug 16, 2011||Fmc Corporation||Dry granulation binders, products, and use thereof|
|US8801847||Dec 20, 2010||Aug 12, 2014||Fmc Corporation||Microcrystalline cellulose compositions|
|US8927609||Nov 30, 2012||Jan 6, 2015||Fmc Corporation||Co-attrited stabilizer composition|
|US8932629||Oct 26, 2007||Jan 13, 2015||Fmc Corporation||Co-processed microcrystalline cellulose and sugar alcohol as an excipient for tablet formulations|
|US9055757||Oct 4, 2012||Jun 16, 2015||Fmc Corporation||Stabilizer composition of co-attrited microcrystalline cellulose and carboxymethylcellulose, method for making, and uses|
|US20030206978 *||Sep 27, 2002||Nov 6, 2003||Bob Sherwood||Agglomerated particles including an active agent coprocessed with silicified microcrystalline cellulose|
|US20050196439 *||Oct 21, 2004||Sep 8, 2005||J. Rettenmaier & Soehne Gmbh + Co. Kg||Process for co-spray drying agents with dry silicified MCC|
|US20060115555 *||Dec 1, 2004||Jun 1, 2006||Foulger Sidney W||Nutritional supplements containing xanthone extracts|
|US20060115556 *||May 12, 2005||Jun 1, 2006||Foulger Sidney W||Nutritional supplement drink containing xanthone extracts|
|US20060228487 *||Apr 11, 2005||Oct 12, 2006||J. Rettenmaier & Söehne GmbH + Co. KG||Methods of combining active agents with augmented microcrystalline cellulose|
|US20070128333 *||Sep 28, 2006||Jun 7, 2007||Tuason Domingo C||Stabilizers and Compositions and Products Comprising Same|
|US20080213360 *||Oct 26, 2007||Sep 4, 2008||Fmc Corporation||Dry granulation binders, products, and use thereof|
|International Classification||A61K47/12, A61K9/20, A61K9/16, A61K47/34, A61K47/32, A61K47/26, A61K47/36, A61K36/00, A61K47/38, A61K47/04|
|Cooperative Classification||A61K36/8962, A61K36/77, B01J2/04, A61K36/82, A61K36/28, A61K2236/51|
|European Classification||A61K36/82, A61K36/77, A61K36/8962, B01J2/04, A61K36/28|
|May 29, 2003||AS||Assignment|
Owner name: FINZELBERG GMBH & CO. KG, GERMANY
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:BERKULIN, WILHELM;THEISSING, KARL-HANS;REEL/FRAME:014116/0880;SIGNING DATES FROM 20030220 TO 20030226
|Jun 23, 2003||AS||Assignment|
Owner name: PENWEST PHARMACEUTICALS CO., NEW YORK
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:FINZELBERG GMBH & CO. KG;REEL/FRAME:014195/0695
Effective date: 20030321
|Feb 17, 2004||AS||Assignment|
Owner name: J. RETTENMAIER & SOEHNE GMBH + CO. KG, GERMANY
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:PENWEST PHARMACEUTICALS CO.;REEL/FRAME:014978/0898
Effective date: 20040116
|Nov 15, 2007||FPAY||Fee payment|
Year of fee payment: 4
|Dec 22, 2011||FPAY||Fee payment|
Year of fee payment: 8
|Jan 29, 2016||REMI||Maintenance fee reminder mailed|
|Jun 22, 2016||LAPS||Lapse for failure to pay maintenance fees|
|Aug 9, 2016||FP||Expired due to failure to pay maintenance fee|
Effective date: 20160622